Treatment seeking patients who are cocaine and alcohol dependent have poor prognosis. While there are no uniquely effective medications, combined pharmaco- and psychotherapy may prove efficacious. Naltrexone (NTX), approved for alcohol dependence, may block cocaine-alcohol rewarding effects at higher doses (> 50 mg/d) but psychotherapeutic context is critical. Our preliminary work indicates potential utility of NTX when combined with Relapse Prevention (RP) therapy and Contingency Management Procedures (CMP). We propose a large, double-blind, placebo-controlled, full factorial study to examine the role of RP + CMP combined with NTX for treatment of cocaine-alcohol dependence. Cocaine-alcohol dependent outpatients (N = 140) will be randomly assigned to NTX 100 mg/d or placebo combined with one of two psychotherapy conditions (RP or RP + CMP). Standardized consent and intake procedures will be followed by a single-blind baseline placebo week and then a 12 week trial with twice weekly visits. Manual-guided RP therapy will be delivered weekly in 60-minute individual sessions. CMP will reinforce abstinence based on cocaine-negative urine screens and negative breath alcohol test results. Medication adherence will be monitored with riboflavin and pill counts. Follow-up assessments will be conducted at 3, 6, 9, and 12 months after treatment termination. Primary efficacy variables will be measures of substance use (i.e., urine screens, Time-Line Follow-Back methods, collateral informants, change in liver enzymes) and retention (i.e., number of sessions attended, time to dropout). Secondary variables will include addiction severity and adverse event measures. A third set of variables will be tested as possible predictors of therapeutic outcomes. These include measures of motivation, self-efficacy, medication compliance, serum 6-beta naltrexol levels, craving, family history of alcohol problems, and severity of dependence. Power is sufficient to test the main hypothesis that NTX 100 mg/d with RP + CMP will reduce cocaine and alcohol use. Secondarily we will: (1) examine outcome variability as a function of individual differences on a range of potential predictors; (2) evaluate relative reinforcement of cocaine and alcohol using an innovative multiple choice measurement strategy; and (3) examine the relationship between cocaine and alcohol use during treatment and follow-up.